PROJECT SUMMARY/ABSTRACT
Ascaris (roundworm) is the most prevalent helminth in the world infecting millions of people living in poverty-
stricken, parasite-endemic regions in low- and middle-income countries (LMICs). Ascaris infects children early
in life and has a highly immunogenic larval migratory phase through the lungs before returning to the intestines
and developing into adult worms. High Ascaris worm burden and significant re-infection rates in children causes
profound life-long morbidity. Using our Ascaris mouse model, our lab discovered that transient Ascaris larval
migration through the lungs leads to chronic structural and functional changes consistent chronic lung disease.
Chronic lung disease in the mouse model was associated with sustained concentrations of Th2 and Th17 cells
in the lungs suggesting on-going immune activation despite infection resolution. The data suggest Ascaris may
be a contributing risk factor for the development of chronic lung disease in parasite-endemic areas. However,
despite our robust Ascaris mouse model findings, mice are a non-native host for ascariasis. Evaluating Ascaris-
induced chronic lung disease in human clinical trials is ideal but challenging due to the complexity of the parasitic
life cycle and the lack of sustainable long-term resources in parasite-endemic regions. In addition to humans,
domestic pigs are a native host for Ascaris spp. Additionally, due to similar lung anatomy, physiology and
immunologic responses pigs are used routinely as animal models of human disease. Furthermore, like human
ascariasis, Ascaris is the most prevalent helminth infection in pigs and has significant consequences on porcine
health. The overall objective of this proposal is to develop a novel, translational porcine model of ascariasis to
evaluate the long-term consequences of Ascaris larval migration through the native host lungs. We hypothesize
that Ascaris larval migration through the lungs of a native host will cause Ascaris-induced chronic lung disease.
The first aim will evaluate the impact of Ascaris larval migration on lung function and structure longitudinally in a
porcine model. We will use human grade physiologic monitoring systems and histopathology to determine
Ascaris-induced chronic lung disease. In the second aim we will characterize the immunologic milieu in the lungs
longitudinally following Ascaris larval migration in a porcine model. Using immunologic assays and RNA
sequencing we will identify key immunologic pathways involved in Ascaris-induced chronic lung disease. This
“One Health” model will provide important information regarding the impact of Ascaris larval migration on both
humans and pigs, leading to improved health within the shared environment. Our findings will be used to identify
novel therapeutic targets to prevent ascariasis in both humans and pigs in parasite-endemic regions globally.